在本研究中，我们在吉西他滨（GEM）的第四氨基位置引入了一种对H2O2敏感的噻唑烷酮基团，通过核磁共振光谱法确认了合成的新目标化合物GEM-ZZQ的化学结构。我们进一步证实了GEM-ZZQ在不同pH值溶液中具有良好的化学稳定性，并且它可以通过H2O2的激活释放GEM。药效学研究表明，与GEM治疗相比，GEM-ZZQ对人类正常上皮细胞的生长抑制效果较弱，而对各种肺癌细胞系的抑制效果与GEM相似。对于对表皮生长因子受体（EGFR）靶向抑制剂奥西美替尼（osimertinib）耐药的肺癌细胞系，与GEM相比，GEM-ZZQ的生长抑制作用较弱。然而，在低剂量组中，GEM-ZZQ与顺铂的联合应用显示出比GEM更好的协同效应。总之，我们通过改变GEM的结构提供了一种新的抗癌化合物GEM-ZZQ，用于治疗肺癌。

In the present study, we introduced the H 2O 2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine (GEM) to synthesize a new target compound named GEM-ZZQ, and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H 2O 2 to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM. For the lung cancer cell lines that are resistant to the epidermal growth factor receptor (EGFR)-targeting inhibitor osimertinib, GEM-ZZQ showed less growth inhibition than GEM; however, GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups. In summary, we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.